Strasbourg, 31 October 2023                                                                             CDBIO(2023)25

STEERING COMMITTEE FOR HUMAN RIGHTS

IN THE FIELDS OF BIOMEDICINE AND HEALTH

(CDBIO)

EQUITABLE AND TIMELY ACCESS

TO APPROPRIATE INNOVATIVE TREATMENTS AND TECHNOLOGIES

IN HEALTHCARE

Discussion paper

prepared the Drafting group, on the basis of a document drafted

by Prof. Kristof Van Assche, Consultant

Table of contents

1.    Introduction. 3

2.    Scope and definitions. 4

2.1.     Scope. 4

2.2.     Definitions. 4

3.    Key differences with conventional treatments and technologies. 5

3.1.     Characteristics of innovative treatments and technologies. 5

3.2.     Levels of decision making. 6

4.    Applicability of the general and procedural principles defined in Recommendation CM/Rec(2023)1  7

4.1.     General principles. 7

4.2.     Procedural principles. 11

5.    Assessing the need for additional principles and suggestions for possible future approaches  16

APPENDIX I: Illustrative overview of innovative treatments and technologies. 19

APPENDIX II: Work done in the Council of Europe and other organisations. 23

APPENDIX III: Analysis of the most relevant work done in other organisations. 29

1.    Introduction

Article 3 of the Convention on Human Rights and Biomedicine requires Parties, taking into account health needs and available resources, to take appropriate measures with a view to providing, within their jurisdiction, equitable access to health care of appropriate quality.

Equitable access should be interpreted in accordance with the meaning provided in Article 3 and clarified in paragraph 25 of its Explanatory Report. In this context, equitable access means first and foremost the absence of discrimination on any ground. Equitable access also implies that, depending on their medical needs and the available resources, individuals should be guaranteed access allowing them to effectively obtain a satisfactory degree of care. This involves removing barriers that may prevent access and providing appropriate support to individuals or groups who may be disadvantaged or exposed to a higher risk of harm to their health. In accordance with the Right to the protection of health enshrined in Article 11 of the European Social Charter (revised), the ultimate goal is health equity – i.e., the absence of avoidable, unfair, or remediable differences among groups of people – where ideally everyone should have a fair opportunity to attain their full health potential and no one should be disadvantaged from achieving this potential.

The principle of equitable access also applies to innovative treatments and technologies. In this regard, the Strategic Action Plan (2020-2025) emphasises that it is essential that these are made available in an equitable and timely manner. The intention was to elaborate a Recommendation on equitable and timely access to innovative treatments and technologies in healthcare systems. In the light of the Covid-19 pandemic and the ethical considerations concerning access to vaccines as a scarce resource, the Committee on Bioethics (DH-BIO) agreed, at its 17th plenary meeting (3-6 November 2020), to develop guidelines to promote equitable access to vaccines and to treatments and equipment. Considering the evolutions in vaccine development, the DH-BIO agreed to first prepare a Statement on Covid-19 and vaccines: Ensuring equitable access to vaccination during the current and future pandemics, which was issued on 21 January 2021. At its 18th plenary meeting (1-4 June 2021), the DH-BIO subsequently agreed to develop guidelines on equitable access to treatments and equipment in a context of scarcity, focusing on critical products the scarcity of which could cause serious harm to patients. These guidelines were included in Recommendation CM/Rec(2023)1 on equitable access to medicinal products and medical equipment in a situation of shortage, adopted on 1 February 2023.

At its 2nd plenary meeting (2-4 November 2022), the Steering Committee for Human Rights in the Fields of Biomedicine and Health (CDBIO), which took over the responsibilities of the DH-BIO, initiated work on Equitable and timely access to innovative treatments and technologies in the healthcare system. At its 3rd plenary meeting (6-9 June 2023), the CDBIO discussed the Concept note on equitable and timely access to innovative treatments and technologies in healthcare (CDBIO/BU(2023)8), noting the factual elements that challenge the decision-making process at the national level. These elements include that clinical evidence supporting safety and efficacy is often limited, making the evidence-based decision-making process uncertain. Other factors relate to the problem of affordability due to high prices charged by manufacturers and, more generally, to the need for an overall assessment of the clinical value and appropriateness for patients in the context of the healthcare system. The CDBIO noted that the scope of the work potentially includes a wide variety of healthcare products, processes, and medical procedures, and supported keeping a high-level strategical view on the issue, not limiting the scope of the work to the case of expensive medicinal products. It was also noted that the term innovative does not necessary endorse benefice for patients and can raise unrealistic expectations. The CDBIO agreed that Recommendation CM/Rec(2023)1 already covers most issues related to equitable access to innovative treatments and technologies. The Committee agreed therefore not to prepare a new draft recommendation but to work on a discussion paper to assess any outstanding ethical issues relevant to innovative treatments and technologies to be taken into account when designing the process. The discussion paper should examine how the general and procedural principles of Recommendation CM/Rec(2023)1 apply to the decision-making processes ensuring equitable access to innovative treatments and technologies. It should also map and briefly analyse the work done by other international organizations such as the WHO, OECD, and the EC to avoid duplication, taken into consideration that the paper should take a human rights patient focus approach.

2.    Scope and definitions

2.1.      Scope

In accordance with the scope defined in Article 2 of Recommendation CM/Rec(2023)1, this discussion paper will focus on access to innovative treatments and technologies used for the medical care of patients with serious or life-threatening health conditions. Therefore, it will not consider innovative treatments and technologies that are typically used outside of that context (e.g., Health applications aimed at empowering patients to modify their lifestyle). Similarly, the discussion paper will only focus on access in a situation of limited availability of resources (shortage). This situation generally applies to innovative treatments and technologies used for serious or life-threatening health conditions, since their access is usually restricted because of limited supply or budgetary constraints.

It should, however, be noted that the general and procedural principles may also be applicable in the context of access to innovative treatments and technologies that are used for other than severe or life-threatening health conditions or outside of situations of scarcity.

This discussion paper will focus on the applicability of CM/Rec(2023)1 on the process of defining and implementing priority-setting standards for access to innovative treatments and technologies. Consequently, it will not consider the possible applicability on the process of reimbursement of innovative treatments and technologies. From the perspective of ensuring equitable access, an obligation on the part of states could be helpful to ensure that their healthcare systems adequately take into consideration innovative treatments and technologies (See below).

2.2.      Definitions

Innovative treatments and technologies refer to treatments and technologies that adopt approaches which depart significantly from conventional medical practices. They incorporate cutting-edge scientific discoveries and breakthroughs in engineering, with the aim of providing new therapeutic possibilities and better quality of healthcare. Innovative treatments and technologies have advanced through the various stages of research and development and have obtained regulatory approval for at least some specific indications or applications. In some cases, these treatments and technologies may already be available as standard treatment options.

Experimental treatments and technologies also use innovative approaches, but they are still in the phase of research, development, or clinical evaluation. These treatments and technologies might involve unknown risks and their effectiveness is often uncertain. Patients typically receive experimental treatments and technologies as participants in clinical trials, when existing treatments and technologies are either unavailable or ineffective. Access may be determined by different actors and subject to other criteria than those that apply to innovative treatments and technologies.

Differentiating between experimental and innovative treatments and technologies may be complex. For instance, with respect to certain treatments and technologies (e.g., immunotherapy, regenerative medicine, and neurotechnology), the boundaries between experimental and innovative may be dynamic, as these treatments and technologies may have received approval for certain uses while at the same time being evaluated for expanded indications and applications or for additional patient populations in the future. In should also be noted that, whereas some innovative treatments and technologies may be available in some countries, they may still be considered experimental or may not be available in other countries. This may be related to differences in regulatory approval processes, healthcare infrastructure and resources, national health priorities, and socio-cultural factors.

3.    Key differences with conventional treatments and technologies

3.1.      Characteristics of innovative treatments and technologies

As compared to conventional treatments and technologies, innovative treatments and technologies (See Appendix I for an illustrative overview) may have certain characteristics that are different or more pronounced.

-       First, innovative treatments and technologies may offer cutting-edge solutions for severe or life-threatening conditions that were previously untreatable or for which conventional treatments or technologies are inadequate. The fact that access may have profound and sometimes even life-saving consequences highlights the particular gravity of decisions on making innovative treatments and technologies available and determining priority setting.

-       Second, innovative treatments and technologies may suffer from a lack of statistical robustness, where the available clinical evidence demonstrating safety and efficacy is not strong or conclusive. This may be caused by the small sample size of clinical trials, high variability in patient responses, bias resulting from the underrepresentation of certain groups, and limited follow-up data about long-term effectiveness and side effects. Lack of robust statistical data may present challenges in determining whether a specific treatment or technology is proven and appropriateness, and therefore in making decisions about their authorisation and reimbursement, as well as in establishing the prioritisation of patients.

-       Third, innovative treatments and technologies can be highly complex and novel in their mechanisms of action. This may pose challenges for decision-makers to fully understand the potential benefits and risks. Especially when treatments and technologies are at the intersection of several disciplines, such as medicine, engineering, and data science, decision-making will necessitate a more extensive interdisciplinary expert engagement to adequately take into account their distinct features and impact.

-       Fourth, in the early stages of introducing an innovative treatment or technology, the assessment of its efficacy and how it compares to existing alternatives can be further complicated by marketing hype, media attention, and unrealistic expectations from patients. Especially when treatments or technologies hold the promise of saving the life or significantly improving the quality of life for patients suffering from previously untreatable conditions, patient advocacy groups may hold different perspectives on what constitutes adequate evidence and equitable access. This may result in lobbying efforts and societal pressure that may create challenges to decision making.

-       Fifth, innovative treatments and technologies may raise more complex ethical issues, have broader societal impacts, and more significantly impact trust in biomedicine than conventional treatments and technologies. These may be related to the impact on the healthcare budget, the need to re-evaluate healthcare priorities, and the introduction of therapies or technologies (e.g., gene editing or emerging biotechnologies) which could give rise to specific human rights challenges or have repercussions on future generations.

-       Sixth, innovative treatments and technologies are often extremely expensive (See Concept note CDBIO/BU(2023)8), raising issues of affordability. The high cost of these innovative treatments and technologies can be a significant barrier to access. For most patients access will therefore be contingent on the reimbursement policies in place within the healthcare system. Decisions on making a specific innovative treatment or technology available will have broader implications for healthcare budgets, which may influence the availability of other healthcare services.

3.2.      Levels of decision making

Decision-making in access to treatments and technologies involves three levels. The first level concerns the decision on authorisation, where the quality, safety, and effectiveness are evaluated, and it is determined whether the treatment or technology meets the medical standards to grant authorisation for use in healthcare. The second level concerns the decision on reimbursement, where it is determined whether the treatment or technology that is authorised for use will be funded or reimbursed and, if so, for what conditions and patient populations. The third level concerns the decision on priority-setting between eligible patients. These three levels of decision-making are interconnected and collectively determine whether and how patients gain access.

Whereas for conventional treatments and technologies reimbursement will often be provided, since cost profiles are generally more manageable, this may be more challenging for innovative treatments and technologies. More importantly, this difference raises two fundamental issues with regard to equitable access.

-       First, since it is often the price that makes the innovative treatment or technology scarce, access will usually depend on the reimbursement policies within the healthcare system. Consequently, for most innovative treatments and technologies patient access will be decided at an earlier stage (i.e., decision on reimbursement) than the one applying to scarce conventional treatments and technologies (i.e., decision on priority-setting). When it is decided that an authorised innovative treatment or technology will not be covered by public health insurance, access will for most patients be practically impossible. In that case, considerations of priority-setting to ensure equitable access may become largely irrelevant. This is especially pertinent in countries where healthcare budget limitations may impede reimbursement of innovative treatments and technologies, rendering most principles outlined in Recommendation CM/Rec(2023)1 practically insignificant.

-       Second, it may not always be clear to what extent the principles outlined in Recommendation CM/Rec(2023)1 are currently applied to the level of decision-making on reimbursement, considering that there is limited transparency in this process. Here the question can be raised whether and, if so, how the procedural and general principles defined in Recommendation CM/Rec(2023)1 may also be extended to that context.

It should be noted that guidance on national healthcare budget expenditure does not fall within the mandate of the CDBIO. However, taking into account the impact that decisions on reimbursement may have, equitable access would require States to ensure that innovative treatments and technologies are properly assessed for their impact on their healthcare system, in accordance with the principles outlined in Recommendation CM/Rec(2023)1.

4.    Applicability of the general and procedural principles defined in Recommendation CM/Rec(2023)1

4.1.      General principles

(a)  Non-discrimination (Article 4)

The general principle applies that no person in need of innovative treatment or technology should a priori be excluded from access to them. In the same way, the principle that discrimination on any ground in terms of access to innovative treatment or technology should be prohibited, is equally relevant in this context.

The characteristics of innovative treatments and technologies do not pose specific challenges here.

Elements such as selection bias, the expensive nature of treatments and technologies, and in certain situations patient advocacy activities can have an adverse effect on the accessibility of specific populations groups. However, since these elements do not constitute direct discrimination, they will be addressed under the principles where they are most pertinent.

(b)  Attention to systematically disadvantaged individuals in relation to health (Art. 5)

The principle that specific attention should be paid to individuals and groups who are systematically disadvantaged in relation to health also holds with regard to access to innovative treatment and technology.

The characteristics of innovative treatments and technologies do not present particular challenges in this context.

(c)  Prioritisation based on medical criteria (Article 6)

The principle that an individual medical assessment should be made before a decision can be taken as to whether an individual should have access, also holds for access to innovative treatment and technology.

This individual medical assessment should be performed on the basis of the four elements listed in Article 6, paragraph 1: (1) the severity of the health condition of the individual concerned and the healthcare needs to address it; (2) the expected effectiveness of the innovative treatment and technology; (3) the possible therapeutic alternatives; and (4) the consequences of the lack of access to the innovative treatment or technology for the health of the individual concerned.

In this assessment, a major concern can be raised about the expected effectiveness of the innovative treatment and technology. Uncertainties may exist about whether innovative treatment and technology will genuinely deliver the expected benefits in terms of patient outcomes, safety, and improvement upon the existing standard of care. For innovative treatment and technology the available clinical evidence is often limited, for instance because the clinical trials conducted to demonstrate safety and efficacy were small, follow-up data about long-term effectiveness and potential side effects are absent, or sufficient comparative data with existing standard treatments or technologies are lacking.

Doubts can also be raised about the generalisability of research findings across different patient populations, especially considering the severe underrepresentation of certain groups in clinical trials. Clinical trials that primarily include homogenous populations and lack adequate representation of, for instance, ethnic minorities, women, older persons, or patients with rare diseases, may result in treatments that are not or less effective or safe for those groups, leading to differences in treatment outcomes. This is especially relevant for innovative treatment where the treatment response may be influenced by both intrinsic factors (e.g., genetic polymorphism, age, gender, height, weight, lean body mass, body composition, and organ dysfunction) and extrinsic factors (e.g., factors associated with the environment and the cultural background of the person).

Another example is algorithmic bias that AI systems frequently suffer from. Since algorithms are often based on clinical data sets where specific subgroups are underrepresented, the use of AI systems in healthcare might be biased against these groups in that they risk being misdiagnosed or presented with ineffective treatments, in this way reinforcing health inequities.

Moreover, during the initial phases of introducing a novel treatment or technology, the assessment of its expected effectiveness and comparison to alternatives can be additionally complicated by marketing hype, media interest, and patient advocacy. Although these concerns may not be unique to innovative treatment and technology, their implications may be more profound, considering their cutting-edge nature, typically high costs, and the frequent application in the medical care of patients with severe or life-threatening health conditions.

After the decision is taken that, on the basis of the individual medical assessment, a patient may be granted access to innovative treatment or technology, but the healthcare system is confronted with a situation of scarcity and several patients urgently need the innovative treatment or technology, priority should be given to minimising the risk of mortality and, subsequently, morbidity.

This is in accordance with the principle set out in Article 6, paragraph 2. Innovative treatments and technologies do not present particular challenges in this context.

(d)  Appropriate support and removal of barriers (Article 7)

In accordance with Article 7, barriers to accessing innovative treatments and technologies should be removed and appropriate support should be given to those individuals or groups who may be disadvantaged or exposed to a higher risk of harm to their health.

Because of the specific characteristics of innovative treatments and technologies, significant barriers to access may exist that are more pronounced as compared to conventional treatments and technologies. These include financial barriers, the digital divide, limited health literacy, lack of infrastructure and trained healthcare professionals, and cultural and language barriers.

-       First, the cost of innovative treatments and technologies can constitute an important barrier to access, in particular for individuals with limited financial means. The price is influenced by high development and production costs, expensive clinical trials and regulatory approval procedures, intellectual property considerations, the level of competition, market demand, and profit margins that are informed by the expected long-term cost savings offered by these treatments and the “willingness to pay” of individuals and society as a whole. The primary factor contributing to the high price is the market analysis, which is often not transparently connected to the proposed price.

Since for most patients availability will depend on the reimbursement policies that are in place in the healthcare system, removal of financial barriers may in the context of innovative treatment and health technology need to involve optimisation of reimbursement policies and control of costs. Reimbursement policies for extremely expensive innovative treatments may take a variety of approaches: reimbursement of treatment that is proven to be clinical and cost effective on the basis of a Health Technology Assessment, developing stricter reimbursement criteria for treatments that would significantly strain the healthcare budget, conditional approval and reimbursement of treatment while data on long-term clinical and cost effectiveness are collected, establishing dedicated funds or programs with strict eligibility criteria, or providing access to compassionate use programs.

Governments can try to control the costs of very expensive innovative treatment and technology, and in this way improve access, in several ways. They can promote transparency in the cost and pricing and establish a mechanism for accountability. They can negotiate with pharmaceutical or biotechnology companies to provide the treatment at a discounted price as determined in a confidential agreement. Governments can also encourage manufacturers to justify high prices with demonstrable clinical value. Alternatively, they can implement reference pricing, where the price of innovative treatment or technology is based on the cost of comparable treatments and technologies. Governments can also increase public funding for research and development in healthcare and encourage competition from generic manufacturers when patents expire.

-       Second, in case of digital or data-driven innovative treatments and technologies, a “digital divide” may emerge between individuals who have and those who don’t have access to digital devices and reliable high-speed internet services. This digital divide may prevent the equitable access of low-resource communities or individuals living in rural areas to technologies including digital therapeutics, telehealth consultations, point-of-care diagnostics, and neurotechnology. This divide can be addressed by strategies involving investment in broadband infrastructure in underserved areas, providing low-cost digital devices to individuals who cannot otherwise afford them, and supporting initiatives to offer affordable internet plans.

-       Third, limited health literacy is an important barrier to accessing innovative treatment and technology. Health literacy (i.e., referring to an individual’s ability to access, understand, appraise, and apply information concerning healthcare, and including health knowledge, practical skills, critical thinking and self-reflective skills, and ethical responsibility) may be limited in certain population groups, such as ethnic minorities, individuals living in poverty, elderly individuals, and patients with chronic conditions. While limited health literacy is already a challenge in traditional healthcare, it is especially problematic when dealing with cutting-edge treatment and technology. Patients with lower health literacy may not be aware of innovative treatment or technology or on how to make use of resources (e.g., clinical trials; financial assistance) and procedures (e.g., referrals; insurance coverage) to access them. They may lack the digital skills necessary to use certain technologies and understand instructions (e.g., in the context of digital therapeutics and telehealth). They may lack the critical skills to assess the reliability and credibility of information on innovative treatment and technology. They may also struggle to comprehend information on the available options, their mechanisms of actions and potential benefits and side effects, and possible test results and treatment recommendations. As a result, patients may find it difficult to make informed decisions among different treatment options. Guidance to improve health literacy is provided in the Guide to health literacy.

-       Fourth, other factors that may hinder access to innovative treatment and technology and may exacerbate health inequities are geographic barriers, and lack of infrastructure and trained healthcare professionals. Innovative treatment and technology typically rely on robust infrastructure, including healthcare facilities with specialised treatment centres, advanced equipment, state-of-the-art technological know-how, and sufficient numbers of trained healthcare professionals. Individuals living in remote or rural areas or in underfunded and underserved areas where this infrastructure is lacking, will not have the ability to benefit from the latest advancements in treatment and medical technology. Taking into account available resources, these barriers may be removed by investment in the required healthcare infrastructure, and in ongoing education and training to ensure that healthcare professionals have the clinical expertise to provide expert care involving innovative treatment and technology. Measures may also need to be taken to retain these trained healthcare professionals in remote, rural, and underserved regions.

-       Fifth, access to innovative treatment and technology can be significantly hindered by cultural and language barriers. Cultural beliefs can influence the acceptance and adoption of innovative treatment and technology, leading individuals to refuse treatments that contradict their cultural or religious values or to delay seeking medical care. Language barriers can hinder effective communication with healthcare providers, in this way preventing full understanding of the implications of innovative treatment or technology and negatively affecting the process of informed consent. Linguistic and cultural barriers may also result in a lack of awareness about innovative treatments and technologies.

To address these barriers and promote equitable access, it is essential that innovative treatments and technologies are developed and designed to ensure inclusivity, that healthcare providers undergo cultural competency training to increase sensitivity to the unique needs of diverse patient populations, that resources are accessible, culturally appropriate, and provided in multiple languages, that interpreters are employed, and that public education and awareness campaigns are set up in culturally sensitive ways and in collaboration with trusted community leaders and organisations. This is in accordance with the principle set out in Article 7.

(e)  Respect for the dignity of persons excluded from access (Article 8)

When, on the basis of the general principles outlined above, a patient does not have access to life-saving innovative treatment or technology (e.g., immunotherapy, regenerative medicine), that person’s dignity should be respected, in accordance with Article 8. In this context, innovative treatments and technologies do not give rise to specific challenges.

Alternative healthcare options should be provided, when available and appropriate. In the absence of these options, the focus should shift to pain and symptom management by offering compassionate and palliative care in accordance with the principles set out in the Guide on the decision-making process regarding medical treatment in end-of-life situations. Healthcare providers should engage in open, honest, and empathetic communication with these patients and these families, to ensure that they understand the medical criteria and reasons behind their exclusion, and the lack of any alternative curative or life-prolonging treatments. A comfortable and supportive environment should be ensured, and psychological, emotional, and spiritual support should be provided to guarantee the best possible quality of life. This is in accordance with the principle set out in Article 8.

4.2.        Procedural principles

To ensure that priority-setting standards for access to innovative treatment and technology are defined and implemented in a way that guarantees equitable access, several procedural principles should be followed. These principles seem to be very similar, if not identical, to those that apply to the process of defining and implementing priority-setting standards for more conventional treatment and technology. These principles may, however, take on greater importance when dealing with innovative treatments and technologies because of their particular characteristics.

(a)  Accountability (Article 9)

In the context of defining and implementing priority-setting standards for access to innovative treatment and technology, it is important that responsibilities are clearly defined, and that the healthcare professionals who will be required to apply these standards as well as the public should be informed on which entities are accountable at the different stages of priority-setting and implementation and on where and how concerns can be addressed regarding decisions on priority-setting. Although the principle is similarly applicable as in the context of more conventional treatment and technology, it is for several reasons of particular importance in the context of innovative treatment and technology.

-       First, making innovative treatment and technology available and setting priority for access can have profound and far-reaching consequences for individual and public health (e.g., if access to potentially life-saving treatment such as immunotherapy or regenerative medicine is denied, or considering that treatment such as gene therapies or involving nanomedicine might have a severe and unforeseeable impact on public health).

-       Second, innovative treatment and the use of novel technologies generally are very expensive, and decisions on resource allocation can have significant implications for the overall sustainability of the healthcare system.

-       Third, considering the complexity and technicality of innovative treatments, decision-making entities include experts from a wide range of disciplines or may need to collaborate with various stakeholders of which some may have their own agendas (e.g., pharmaceutical companies and patient advocacy groups) (See also Concept note CDBIO/BU(2023)8).

Transparency with regard to responsibilities at the different stages of decision-making is therefore even more important in the context of innovative treatment and technology. It should, however, be noted that the availability of very expensive innovative treatment (e.g., gene therapies, CAR T-cell therapies, immunotherapies, and precision medicine) will to a large extent depend on negotiations with pharmaceutical or biotechnology companies. Considering that the price is determined in accordance with market mechanisms, accountability will depend on clearly identifying the entity responsible for these negotiations and their outcomes.

(b)  Reasonableness and relevance (Article 10)

Policies for priority-setting in access to innovative treatment and technology need to be based on the best available evidence. This evidence should rely on parameters that are relevant, measurable, clear, objective, and consistent. This principle, which applies to medicinal products and medical equipment more broadly, may pose specific challenges in the context of priority-setting standards for access to innovative treatment and technology.

-       First, as compared to more established therapies, innovative treatments and technologies frequently lack a robust body of evidence on safety and effectiveness. This shortage of data, further compounded by the ongoing nature of clinical trials for many innovative treatments and the uncertainty surrounding their long-term outcomes, presents challenges in constructing sound arguments for their integration into the healthcare system and in determining the prioritisation of patients.

-       Second, innovative treatments can be highly complex and novel in their mechanisms of action, making it difficult for decision-makers to fully understand the potential benefits and risks.

-       Third, confronted with the rapid pace of innovation, decision-makers must frequently revise their reasonable arguments to incorporate new evidence and newly emerging treatments, technologies, and applications.

In this light, what is “reasonable” may be much more difficult to establish. The reason is that policies for priority-setting in access to innovative treatment and technology are generally developed on the basis of incomplete evidence, against a background of scientific uncertainty and an incomplete understanding of underlying mechanisms and long-term impact, and in a rapidly changing landscape where alternatives and new applications become available. In addition, what is “reasonable” may be different depending on the perspectives of the different stakeholders (as explained in the Concept note CDBIO/BU(2023)8, table 2). Moreover, when assessing the reasonableness of an innovative treatment, especially one that initially offers limited benefits, it may be essential to consider its future potential. Through experiences gained in their clinical implementation, innovative treatments may evolve to provide significantly improved outcomes (e.g., innovative oncology treatment which initially only offer a few weeks of life prolongation but may later advance to provide many years of life prolongation).

The principle that measures should be taken to ensure that the evidence that is taken into account is considered as relevant and fair to the greatest extent possible by all affected parties, is also applicable to the context of innovative treatment and technology. As compared to more traditional therapies, particular challenges may also arise here. Considering that many innovative treatments and technologies hold the promise of offering life-saving or life-changing improvements where often no alternative exists, patient advocacy groups and the public, often driven by media hype and unrealistic expectations, may hold a different view on what is relevant and fair. This can create challenges in maintaining a balanced and evidence-based approach to decision-making. To address these challenges, it may be important to manage patient and public expectations through public debate (cf. using the Guide to public debate on human rights and biomedicine) and to seek an independent assessment of the relevance of the evidence and of the fairness of certain policy options by engaging interdisciplinary teams of impartial experts, including individuals with the required technical expertise and individuals focusing on the ethical and societal impact (e.g., bioethicists).

(c)  Inclusiveness (Article 11)

The process of developing, refining, and reviewing priority-settings standards for access to innovative treatment and technology should be inclusive to ensure that the views of all parties who may be affected by the resulting decisions are represented. Meaningful engagement, in particular of groups that are disadvantaged or exposed to a higher risk of harm to their health, is vital to ensure fulfilment of the general principles that specific attention is paid to individuals and groups who are disadvantaged in relation to health (Article 5) and that appropriate support can be provided and barriers can be removed (Article 7). It is also important to improve transparency of decisions and ensure that educational tools and communication materials are tailored to the needs of healthcare professionals and the public, in accordance with the procedural principle enshrined in Article 13. Finally, this inclusiveness will also help to ensure that decisions are part of a broader deliberative democratic process involving all groups that may bear the consequences of these decisions. Guidance to ensure an effective public dialogue on the conditions for access to innovative treatment and technology can be found in the Guide to public debate on human rights and biomedicine.

While the principle of inclusiveness is important in the context of medicinal products and medical equipment, it is even more critical in the context of innovative treatment and technology.

-       The first reason is the complexity of innovative treatment and technology, which often incorporate cutting-edge scientific discoveries, breakthroughs in engineering, and digital tools. Input from a wide range of experts, clinicians, and patients is essential to take into account all relevant perspectives on possible benefits, risks, and implications, especially in light of the uncertainties, the evolving evidence, and the rapid advancements associated with innovative treatments and technologies.

-       Second, the introduction of innovative treatments and technologies may have an impact on a greater diversity of stakeholders. For instance, these treatments and technologies are often at the intersection of several disciplines, including medicine, engineering, and data science.

-       Third, they also may have a wider societal impact than their immediate clinical application, for instance because they can raise ethical, legal, and societal questions that are more prominent (e.g., discussions on who to prioritise may be more contentious with regard to access to life-saving innovative treatment than with regard to conventional treatment, and discussions on making available or reimbursing innovative treatment such as gene therapies or involving nanomedicine may raise ethical issues (e.g., potentially including an impact on future generations)) and healthcare budget concerns that do not exist or are less relevant in conventional treatment.

-       Fourth, engagement of the public may also be more important, since innovative treatments and technologies may raise more concerns and might more fundamentally impact trust in biomedicine than conventional treatments and technologies. This may require the collection of data on how different groups may be affected by priority-setting decisions and to identify potential disparities that require the adjustment of policies, in accordance with Article 14.

It should be noted that the need to involve a broader range of stakeholders may also result in additional challenges. First, this great diversity may make it more difficult to ensure that all relevant perspectives are adequately represented. Second, ensuring that non-experts, including patient groups, have a meaningful say in the process of decision-making will be much more resource-intensive and demanding in the context of innovative treatments and technologies, considering that these are technologically very complex and rapidly evolving as well as potentially contentious and generating high expectations and media hype. Substantial efforts will be needed to inform these stakeholders about the available evidence and to educate them about the nuances of the decision-making process.

(d)  Consistency (Article 12)

The principle that policies that define and implement priority-setting standards should be applied in a consistent way is also essential in the context of innovative treatment and technology. The consistent application of policies based on predetermined criteria helps to prevent discrimination, promotes transparency in decision-making and, in this way, enhances trust in the healthcare system and decision-makers, enables the effective allocation of scarce healthcare resources, and provides predictability for patients and healthcare providers.

The principle of consistency may be more challenging in the context of innovative treatments and technologies as compared to the context of more conventional treatment and technology, considering that policies may need frequent and ongoing adaptation in the light of rapid technological advancements and a changing evidence base.

The policies that define and implement priority-setting standards should be designed to prevent corruption, arbitrary exceptions, access on the basis of financial means, activities such as lobbying and political interference. This becomes particularly relevant in the context of innovative treatments and technology, where rapid access can be a matter of life and death. Patients, their families, and patient advocacy groups may intensify lobbying efforts to secure approvals, reimbursements, or exceptional access to novel treatments.

(e)  Transparency and communication of decisions (Article 13)

Transparency and communication of decisions is especially relevant in the context of innovative treatment and technology, considering the complexity of innovative treatment and technology, the particular ethical and societal challenges that they raise, the inflated patient and public expectations about their effectiveness, and their budgetary implications, which can affect the accessibility of healthcare alternatives.

Moreover, making the objectives, standards, and reasons of the proposed priority-setting standards publicly accessible is crucial to ensure transparency of the decision-making process. It allows patients and the public to understand why and how priorities were determined and fosters accountability as decision-makers know that their decisions will be subject to public scrutiny. In addition, it empowers patients to effectively advocate for themselves when discussing treatment options with healthcare providers. Moreover, transparency is essential to build trust, since persons who understand the decision-making process and the resulting priority-setting are more likely to trust that decisions are being made in their best interest, focus on promoting equitable access, and are based on the latest evidence. Public access also facilitates feedback from patients and the public, which can be valuable to refine and improve priority-setting standards over time.

Taking into account the complexity of innovative treatment and technology, the challenges that they raise, and the unrealistic expectations that may exist, it is important that information on prioritisation is clear, accurate, and understandable. Information should be presented in a way that is free from technical or medical jargon and easy to comprehend. It should be adapted to varying educational levels, literacy skills, and language proficiencies, with specific attention to those with limited literacy or confronted with language barriers. Communication materials should be made available in a variety of formats, translated into relevant languages, and distributed through easily accessible platforms.

Clear and honest communication about the realities of limited availability is especially crucial in the context of innovative treatment and technology. These may represent cutting-edge solutions for severe or life-threatening conditions and, consequently, limited availability can have life-changing or life-threatening consequences. Transparent communication about limited availability will also help patients and healthcare providers in making informed decisions about the best alternative treatment options. In addition, if individuals feel that they are being provided with accurate information even in challenging circumstances, this helps to maintain trust in the healthcare system. Moreover, making everyone aware of the challenges related to limited availability will reduce the likelihood that some individuals benefit unfairly through preferential access to undisclosed information.

(f)   Review (Article 14)

Mechanisms for providing feedback on decisions regarding the prioritisation of access to innovative treatment and technology are essential to ensure equitable access. This is more critical for innovative treatment and technology as compared to conventional treatment and technology since the former may involve cutting-edge technologies and may be introduced under scientific uncertainty and with only limited availability of clinical data. Collecting feedback is therefore essential to further refine access criteria as new evidence becomes available.

The introduction of interim and retrospective review processes is equally crucial for ensuring equitable access to innovative treatment and technology. Frequent reviews ensure that access standards can adapt to emerging evidence and technological advancements, maintaining access criteria that are evidence-based and up to date. Monitoring possibilities to increase availability of innovative treatment and technology may also be paramount.

Review models may also include equity impact assessments to evaluate how different groups may be affected by priority-setting decisions and to identify potential disparities that require the adjustment of policies.

5.    Assessing the need for additional principles and suggestions for possible future approaches

This examination of the general and procedural principles of Recommendation CM/Rec(2023)1 to innovative treatments and healthcare technologies indicates that they are similarly applicable to access to innovative treatments and technologies. With regard to several of these principles, no particular challenges are raised in the context of innovative treatments and technologies. By contrast, in light of the specific characteristics of innovative treatments and technologies, other principles may be especially relevant or may raise particular challenges.

Taking this into consideration, three possible approaches are possible:

a.    A new Recommendation on equitable access to appropriate innovative treatments and technologies

This approach would enable to highlight the particular aspects where specific attention may need to be paid in the context of innovative treatments and technologies. On the basis of the literature, the following principles and elements could be usefully included in such a Recommendation:

1.    Decision-making processes should incorporate the principle of adaptability and flexibility (principle of adaptive governance): standards and criteria should be flexible enough to accommodate evolving medical knowledge, the rapid pace of technological advancements in healthcare, and changing healthcare contexts, and should allow real-time data collection and integration.

2.    Decision-making processes should include mechanisms for continuous monitoring and evaluation of the impacts of innovative treatments and technologies over time, considering the potentially long-lasting and uncertain effects, which may require adjustments of priority-setting standards.

3.    Decision-making processes should focus on extensive patient education and a more active role of the public and patients, considering the special characteristics and impact of innovative treatments and technologies.

4.    Decision-making processes should focus on broad interdisciplinary expert involvement to take into account the special characteristics and impact of these treatments and technologies.

5.    Decision-making processes should focus on resource efficiency and allocation strategies, considering their frequently high costs, uncertain outcomes, and major impact on the health budget and the availability of other healthcare options.

Although a new Recommendation might provide the opportunity to emphasise how the characteristics of innovative treatments and technologies may impact decision-making and equitable access, the drafting group does not suggest following this approach. The main reason is that, whereas the organisation and structure of such a Recommendation would be better tailored to the context of innovative treatments and technologies, all of the special considerations already seem to be adequately addressed under the principles defined in Recommendation CM/Rec(2023)1. In this respect, principles such as prioritisation based on medical criteria (Article 6), appropriate support and removal of barriers (Article 7), accountability (Article 9), reasonableness and relevance (Article 10), inclusiveness (Article 11), transparency and communication of decisions (Article 13), and review (Article 14) may be of particular relevance, but do not need to be modified when applied to this context.

As indicated above, one exception may be the principle, specific to innovative treatments and technologies, recommending States to ensure that innovative treatments and technologies are properly taken into consideration and assessed for their impact in the context of their healthcare system, in accordance with the principles outlined in Recommendation CM/Rec(2023)1. However, this type of guidance may not fall within the mandate of the CDBIO.

b.    A position paper, white paper or report

A position paper, white paper or report may allow to describe in more detail how Recommendation CM/Rec(2023)1 is applicable to the context of equitable access to innovative treatments and technologies, while also elaborating on the challenges and the solutions, and, where useful, integrating the relevant elements from the Statement on Covid-19 and vaccines and from the Guide to health literacy, the Guide on the decision-making process regarding medical treatment in end-of-life situations, and the Guide to public debate on human rights and biomedicine, so as that provide the complete picture.

c.    Other efforts to promote equitable access to innovative treatments and technologies

Other efforts could be taken to promote equitable access to innovative treatments and technologies together with other bodies in and outside of the Council of Europe, noting that providing guidance on reimbursement may not fall within the remit of the CDBIO.

APPENDIX I: Illustrative overview of innovative treatments and technologies

Here we present a selection of examples of innovative treatments and technologies to facilitate the understanding of the principles. The overview provides a sense of the broad spectrum of treatments and technologies available. Recognising the rapid pace of medical advancements, some examples are also provided of experimental treatments and technologies, considering that, when these would be authorised, the principles will become applicable.

APPENDIX II: Work done in the Council of Europe and other organisations

List of documents

COUNCIL OF EUROPE

CDBIO – Guide to health literacy contributing to trust building and equitable access to healthcare (2023)

CDBIO – Statement - COVID-19 and vaccines: Ensuring equitable access to vaccination during the current and future pandemics (2021)

CDBIO – Guide to public debate on human rights and biomedicine (2020)

CDBIO – Strategic action plan on human rights and technologies in biomedicine (2020-2025) (2019)

CDBIO – Report on Ethical Issues Raised by Emerging Sciences and Technologies (2015)

CDBIO – From Bio to NBIC convergence – From Medical Practice to Daily Life (2014)

CM/Rec(2023)1 of the Committee of Ministers to the member States on Equitable access to medicinal products and medical equipment in a situation of shortage

CM/Rec(2016)8 of the Committee of Ministers to the member States on the processing of personal health-related data for insurance purposes, including data resulting from genetic tests

CM/Rec(2016)6 of the Committee of Ministers to member States on research on biological materials of human origin

CM/Rec(2012)8 of the Committee of Ministers to member States on the implementation of good governance principles in health systems

CM/Rec(2010)11 of the Committee of Ministers to member states on the impact of genetics on the organisation of health care services and training of health professionals

CM/Rec(2010)6 of the Committee of Ministers to member states on good governance in health systems

PACE Report The use of new genetic technologies in human beings (2017)

Recommendation The use of new genetic technologies in human beings (2017)

PACE Report Technological convergence, artificial intelligence and human rights (2017)

Resolution Technological convergence, artificial intelligence and human rights (2017)

PACE Report Public health and the interests of the pharmaceutical industry: how to guarantee the primacy of public health interests? (2015)

Resolution Public health and the interests of the pharmaceutical industry: how to guarantee the primacy of public health interests? (2015)

PACE Report Equal access to health care (2013)

Recommendation Equal access to health care (2013)

Resolution Equal access to health care (2013)

PACE Report Nanotechnology: balancing benefits and risks to public health and the environment (2013)

Recommendation Nanotechnology: balancing benefits and risks to public health and the environment (2013)

OECD

Exploring the feasibility of monitoring access to novel medicines: A pilot study in EU Member States (2023) + Supplementary material

Exploring the consequences of greater price transparency on the dynamics of pharmaceutical markets (2022) + Supplementary material

Addressing challenges in access to oncology medicines (2020)

Challenges in access to oncology medicines (2020)

Performance-based managed entry agreements for new medicines (2020)

Recommendation of the Council on Artificial Intelligence(2019)

Recommendation of the Council on Responsible Innovation in Neurotechnology (2019)

Health for Everyone? Social Inequalities in Health and Health Systems (2019)

Pharmaceutical Innovation and Access to Medicines (2018)

Issues in Neurotechnology Governance (2018)

Gene Editing in an International Context (2018)

Report on Statistics and Indicators of Biotechnology and Nanotechnology (2018)

Gene Editing for Advanced Therapies: Governance, Policy and Society (2018)

Recommendation of the OECD Council on Health Data Governance (2017)

New Health Technologies: Managing Access, Value and Sustainability (2017)

Council Recommendation on Health Data Governance (2016)

How OECD health systems define the range of good and services to be financed collectively (2016)

Health Data Governance: Privacy, Monitoring and Research (2015)

Improving Health Sector Efficiency. The Role of Information and Communication Technologies(2010)

Nanotechnology: An Overview Based on Indicators and Statistics (2009)

UNESCO

The risks and challenges of neurotechnologies for human rights (2023)

Unveiling the neurotechnology landscape: Scientific advancements innovations and major trends (2023)

Ethical impact assessment: A tool of the Recommendation on the Ethics of Artificial Intelligence (2023)

Readiness assessment methodology: A tool of the Recommendation on the Ethics of Artificial Intelligence (2023)

UNESCO’s Recommendation on the Ethics of Artificial Intelligence: Key facts (2023)

Recommendation on the Ethics of Artificial Intelligence (2021)

Report of the IBC on ethical issues of neurotechnology (2021)

Report of the IBC on the principle of protecting future generations (2021)

Report of the IBC on assisted reproductive technologies (ART) and parenthood (2019)

Report of the IBC on the Principle of Individual Responsibility as related to Health (2019)

Report of World Commission on the Ethics of Scientific Knowledge and Technology (COMEST) on Robotics Ethics (2017)

Report of the IBC on Big Data and Health (2017)

Report of the IBC on the Principle of the Sharing of Benefits (2015)

Report of the IBC on Updating Its Reflection on the Human Genome and Human Rights (2015)

Report of the IBC on the Principle of Non-Discrimination and Non-Stigmatization (2014) 

Report of the IBC on Traditional Medicine Systems and their Ethical Implications (2013)

The Principle of Respect for Human Vulnerability and Personal Integrity. Report of the IBC (2013)

Report of the IBC on social responsibility and health (2010)

WHO

Human genome editing. A framework for governance (2021)

Human genome editing. Recommendations (2021)

Big data and artificial intelligence for achieving universal health coverage: an international consultation on ethics (2018)

Promoting access, quality and innovation to save and improve lives: essential medicines and health products (2016)

Making fair choices on the path to universal health coverage (2014)

EUROPEAN COMMISSION

Addressing health inequalities in the European Union (2020)

AI and Ethics in the Health Innovation Community (2019)

Ethics Guidelines for Trustworthy AI (2019)

Commission staff working document Accompanying the document Communication from the Commission on enabling the digital transformation of health and care in the Digital Single Market (2018)

Study on cross-border health services: enhancing information provision to patients (2018)

Inequalities in access to healthcare - A study of national policies (2018)

A new drive for primary care in Europe: rethinking the assessment tools and methodologies (2018)

Implementation of the right to health care under the UN Convention on the rights of the child (2017)

Mental health in all policies (2017)

Towards Community-based and socially inclusive mental health care (2017)

EU One Health Action Plan against Antimicrobial Resistance (2017)

EU Guidelines on the prudent use of antimicrobials in human health (2017)

Strategic Plan 2016-2020 of the Commission’s Directorate-General for Health and Food Safety (2016)

Study on Big Data in Public Health, Telemedine and Healthcare (2016)

2016 report on access to mental health care in Europe (2016)

Commission Communication: On endocrine disruptors (2016)

Report on the sustainable use of biocides (2016)

European framework for action on mental health and wellbeing (2016)

Council Conclusions on “Supporting people living with dementia: improving care policies and practices”  (2015)

Recommendation on cross-border genetic testing of rare diseases in the European Union (2015)

Scoping study on communication to address and prevent chronic diseases (2015)

Study concerning the review and mapping of continuous professional development and lifelong learning for health professionals in the EU (2015)

European Commission Expert Group on biobanks. Biobanks for Europe - A Challenge for Governance (2015)

Commission Communication: On effective, accessible and resilient health systems (2014)

Implementation report on the Commission Communication on a European initiative on Alzheimer's disease and other dementias (2014)

Implementation report on the Commission Communication and Council Recommendation on rare diseases (2014)

Roma Health Report: Health status of the Roma population - Data collection in the Member States of the European Union (2014)

Road Map - Action Plan Against the rising threats from Antimicrobial Resistance (2014)

Obesity and inequities - Guidance for addressing inequities in overweight and obesity (2014)

EU Action Plan on Childhood Obesity 2014-2020 (2014)

Health inequalities in the EU (2013)

Reflection process on modern, responsive and sustainable health systems (2013)

Commission staff working document: Investing in health (2013)

Commission staff working document: Report on health inequalities in the European Union (2013)

Innovative approaches for chronic diseases in public health and healthcare systems (2013)

Staff Working Document Report on health inequalities in the European Union (2013)

Council Conclusions 2012/C 396/02 on Healthy Ageing across the Lifecycle (2012)

eHealth Action Plan 2012-2020 (2012)

Council conclusions on ‘The European Pact for Mental Health and Well-being: results and future action’ (2011)

European Parliament resolution of 19 January 2011 on a European initiative on Alzheimer's disease and other dementias (2011)

Reducing Health Inequalities in the European Union (2010)

Comparative Analysis of Medically Assisted Reproduction in the EU: Regulation and Technologies (2010)

Background Document Solidarity in health: Reducing health inequalities in the EU (2009)

Communication from the Commission on Solidarity in health: Reducing health inequalities in the EU (2009)

EGE

Values for the Future: The Role of Ethics in European and Global Governance (2021)

Statement on Artificial Intelligence, Robotics and ‘Autonomous’ Systems (2018)

Statement on Gene Editing (2016)

The Ethical Implications of New Health Technologies and Citizen Participation (2015)

Statement on Research Integrity (2015)

Ethics of Security and Surveillance Technologies (2014)

Statement on Clinical Trials (2013)

Ethics of information and communication technologies (2012)

Ethics of synthetic biology (2009)

Ethical aspects of nanomedicine (2007)

Ethical aspects of ICT Implants in the Human Body (2005)

Nuffield Council on Bioethics

DNA.I. Early findings and emerging questions on the use of AI in genomics (2023)

Ethics in genomics healthcare & research: Building connections & sharing best practice, Summary report (2023)

Joint Statement on the Ethics of Heritable Human Genome Editing (2020)

Genome editing and human reproduction: social and ethical issues (2018)

Human embryo culture: Discussions concerning the statutory time limit for maintaining human embryos in culture in the light of some recent scientific developments (2017)

Non-invasive prenatal testing: ethical issues(2017)

Genome editing: an ethical review (2016)

(un)natural: Ideas about naturalness in public and political debates about science, technology and medicine (2015)

Children and clinical research: ethical issues(2015)

The collection, linking and use of data in biomedical research and health care: ethical issues (2015)

Novel neurotechnologies: intervening in the brain (2013)

Donor conception: ethical aspects of information sharing (2013)

Emerging biotechnologies: technology, choice and the public good (2012)

Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review (2012)

Solidarity: reflections on an emerging concept in bioethics (2011)

Human bodies: donation for medicine and research(2011)

Medical profiling and online medicine: the ethics of 'personalised healthcare' in a consumer age (2010)

Dementia: ethical issues (2009)

Public health: ethical issues (2007)

Critical care decisions in fetal and neonatal medicine: ethical issues (2006)

Pharmacogenetics: ethical issues (2003)

Genetics and human behaviour: the ethical context (2002)

The ethics of patenting DNA: a discussion paper(2002)

Stem cell therapy: the ethical issues (2000)

Mental disorders and genetics: the ethical context (1998)

Animal-to-human transplants: the ethics of xenotransplantation (1996)

Human tissue: ethical and legal issues (1995)

Genetic screening: ethical issues (1993)

DEUTSCHER ETHIKRAT

Mensch und Maschine – Herausforderungen durch Künstliche Intelligenz (2023) 

Joint Statement on the Ethics of Heritable Human Genome Editing (2020)

Robotik für gute Pflege (2020)

Eingriffe in die menschliche Keimbahn (2019)

Big Data und Gesundheit (2018)

Global Health, Global Ethics, Global Justice (2018)

Big Data und Gesundheit – Datensouveränität als informationelle Freiheitsgestaltung (2017)

Keimbahneingriffe am menschlichen Embryo: Deutscher Ethikrat fordert globalen politischen Diskurs und internationale Regulierung (2017)

Stammzellforschung – Neue Herausforderungen für das Klonverbot und den Umgang mit artifiziell erzeugten Keimzellen? (2014)

Die Zukunft der genetischen Diagnostik – von der Forschung in die klinische Anwendung (2013)

Werkstatt Leben: Bedeutung der Synthetischen Biologie für Wissenschaft und Gesellschaft (2013)

Personalisierte Medizin – der Patient als Nutznießer oder Opfer? (2013)

COMITE CONSULTATIF NATIONAL D'ÉTHIQUE

Diagnostic médical et intelligence artificielle : Enjeux éthiques (2022)

« l‘eugénisme, de quoi parle-t-on ? » (2021)

« Accès aux innovations thérapeutiques : Enjeux éthiques » (2021)

Joint Statement on the Ethics of Heritable Human Genome Editing (2020)

Enjeux éthiques des modifications ciblées du génome : entre espoir et vigilance (2019)

Avis du CCNE sur les demandes sociétales de recours à l’assistance médicale à la procréation (AMP) (2017)

Réflexion éthique sur l’évolution des tests génétiques liée au séquençage de l’ADN humain à très haut débit (2016)

Recours aux techniques biomédicales en vue de « neuro-amélioration » chez la personne non malade: enjeux éthiques (2013)

Enjeux éthiques de la neuroimagerie fonctionnelle(2012)

APPENDIX III: Analysis of the most relevant work done in other organisations

A.    General findings

Work done in other organisation focuses primarily on: (1) the general principle that equitable access should be ensured (with special attention to the principle of non-discrimination); (2) challenges related to affordability and suggestions to improve affordability; (3) challenges related to the (lack of) evidence base; and (4) active involvement of patients and their representatives in decision making.

These discussions broadly concern: Non-discrimination (Article 4); Prioritisation based on medical criteria (Article 6); Appropriate support and removal of barriers (Article 7); Reasonableness and relevance (Article 10); and Inclusiveness (Article 11). Except for the issue of affordability (Appropriate support and removal of barriers (Article 7)) no in-depth discussion or detailed suggestions on the issue of equitable access to innovative treatments and equipments are found.

B.    Details

1.    OECD

-          Exploring the feasibility of monitoring access to novel medicines: A pilot study in EU Member States (2023) + Supplementary material

o   equity: importance of ensuring that all individuals, irrespective of socio-economic background or location, can access benefits of novel medicines (with specific attention to medicines for rare diseases)

o   affordability:

§  for most novel medicines, prices are beyond the reach of individuals paying out-of-pocket, making third-party funding crucial

§  in many OECD countries, prescription medicines are partially or fully covered by government or social health insurance programs (conditions of coverage and co-payments and deductibles vary)

·         discussion of indicators to explore affordability of novel medicines

·         need for transparency in pricing and reimbursement: measurement of affordability complicated by confidential agreements or managed entry agreements (70% of products) (cf. Exploring the consequences of greater price transparency on the dynamics of pharmaceutical markets (2022))

o   evidence base:

§  suggestion to adopt Coverage with Evidence Development, where real-world effectiveness of novel medicine is continually evaluated after market introduction

§  solid scientific evidence depends on transparent clinical trials + big data

-          Addressing challenges in access to oncology medicines (2020) + Challenges in access to oncology medicines (2020)

o   equity:

§  challenges in access to oncology medicines include shortages, supply interruptions, limitations in availability and coverage, government priority-setting, and funding arrangements

§  access to oncology medicines should not be limited by socioeconomic, geographic, or demographic factors

§  ensuring access to all cancer patients can reduce disparities

§  access to oncology medicines varies significantly across OECD countries (US, Denmark, and Germany highest proportions of approved and covered oncology medicines)

§  access impacted by cost-sharing mechanisms: high co-payments can lead to impaired access or catastrophic health spending (US; Korea)

§  suggestion to perform utilisation tracking of oncology medicines to assess actual uptake and differences in access across regions and coverage programs

o   affordability:

§  high launch prices of oncology medicines and increase in number of patients pose challenges to affordability and sustainability of access, even in wealthy countries

§  suggestion to minimise or eliminate co-payments to reduce impact of costs on cancer patients, or to apply fixed co-payments instead of co-insurance

§  suggestion to provide safety nets to preserve affordability

o   evidence base:

§  suggestion to reduce uncertainty in clinical benefit assessments of oncology medicines by improving collaboration and data sharing between countries (e.g., building multi-country registries; collaboration between pharmaceutical companies, regulators, and health technology assessment entities).

§  suggestion to use managed entry agreements based on real-life performance (cf. Performance-based managed entry agreements for new medicines (2020))

-          Recommendation of the Council on Responsible Innovation in Neurotechnology (2019)

1. Promote responsible innovation in neurotechnology to address health challenges. To this end, relevant actors should:

a) First and foremost, promote beneficial applications of neurotechnology for health and foster research and development to further this aim.

b) Integrate ethical considerations and take into account public values and concerns at the planning stage and design phase of technological development.

c) Foster alignment of public support and economic incentives for neurotechnology innovation with the greatest health needs. 

d) Avoid harm, and show due regard for human rights and societal values, especially privacy, cognitive liberty, and autonomy of individuals.

e) Prevent neurotechnology innovation that seeks to affect freedom and self-determination, particularly where this would foster or exacerbate bias for discrimination or exclusion.

f) Encourage greater awareness of existing systems of oversight and, where appropriate, evaluate and work towards adapting existing laws and regulations for medical practice and research for application to activities involving neurotechnology.

3. Promote the inclusivity of neurotechnology for health. In order to achieve such inclusivity, relevant actors should: 

a) Strive to ensure neurotechnology is both developed for and available to those in need.  

b) Promote an enabling policy environment that advances the inclusion of underrepresented populations including, inter alia, social and economic populations, as well as sex- and age-specific groups, in neurotechnology research and development. 

c) Take into account the diversity of cultures and strive to minimise inequalities with respect to, inter alia, socio-economic, cultural norms, in the development and use of neurotechnology.

5. Enable societal deliberation on neurotechnology. In order to enable such deliberation, relevant actors should: 

a) Promote open communication across expert communities and with the public to promote neurotechnology literacy and the exchange of information and knowledge.  

b) Engage in multi-stakeholder dialogues and deliberation to ensure diverse inputs into decision-making processes, public policy and governance. 

c) Ensure that the results of formal dialogues are considered and taken into account in decision-making wherever possible.

d) Ensure processes for engaging stakeholders are fair, transparent, and predictable. 

e) Encourage transparent processes of technology appraisal to deepen and inform public debate about the longer-term trajectory of neurotechnology.

-          Health for Everyone? Social Inequalities in Health and Health Systems (2019)

o   focus on inequalities in health and health systems, not specifically in access to innovative treatments and technologies: socio-economic differences in exposure to risk factors to health, health status, utilisation of health services, unmet health care needs and coverage

-          Pharmaceutical Innovation and Access to Medicines (2018)

o   challenges:

§  in oncology and certain rare diseases many new medicines target small population groups and command high prices that may not be justified by their health benefits

§  countries may be ill-prepared for the arrival of novel medicines targeting wide population groups. due to budget impact of treating all eligible patients

§  innovation is lacking in certain areas of high-unmet need (e.g., new antimicrobials, non-vascular dementia, and some rare diseases)

§  trust between payers, civil society and pharmaceutical companies has been eroded

o   suggestions to improve affordability

§  maximising value from expenditure

§  ensuring access in countries at different levels of development by applying differential pricing (more affluent countries pay higher prices than poorer countries ensuring sufficient profits to make further investments in R&D)

§  development and application by public payers of transparent criteria for determining willingness to pay so as to ensure that coverage and pricing decisions are understood and accepted by all parties

·         criteria could include not only cost-effectiveness, but also budget impact and equity considerations

·         payers and general public need better understanding of costs involved in developing new medicines and magnitude of returns investors and companies earn

§  fostering competition to improve efficiency of pharmaceutical spending and provide incentives to innovate

§  developing push incentives targeting product development addressing unmet medical needs and attaching access conditions to public funding of R&D

§  increasing trust among stakeholders and improve alignment of industry R&D with societal priorities by promoting better communication and dialogue between payers, policy makers, pharmaceutical companies, and the general public

§  facilitating cooperation in health technology assessment

§  encouraging cooperation in price negotiations, contracting or procurement

§  assessing performance of medicines in routine clinical practice to adjust coverage conditions and prices

§  increasing price transparency in pharmaceutical markets, by indicating publicly existence of pricing agreements, by ex-post and transparent rebates for public payers, and by horizon scanning activities to better prepare for market launches, adoption of new technologies, as well as information on patent expiries and loss of market exclusivity

§  optimising use of performance-based Managed Entry Agreements for products whose effectiveness or cost-effectiveness is highly uncertain at time of launch

-          Gene Editing for Advanced Therapies: Governance, Policy and Society (2018)

o   equity:

§  reimbursement models may operate as one of the most significant barriers for uptake of advanced therapies

§  need to examine reimbursement models utilised by governments and the private sector, as access is intrinsically coupled to willingness to pay

-          New Health Technologies: Managing Access, Value and Sustainability (2017)

o   affordability:        

§  health technology continues to have expansionary effect on volume of care and on expenditure

§  uptake of medical technology, including devices, is principal driver of health expenditure growth

§  new business model emerging where companies claim high prices for medicines targeting small populations affected by severe diseases

§  governments and stakeholders need to reflect on new ways to pay for patient pathways to ensure equitable access to personalised treatments and link payments to health outcomes

o   evidence base:

§  evidence behind technology in early phases of development is generally not strong enough for adequate health care system intervention

§  at time of market entry and assessment for reimbursement, information on absolute effectiveness, comparative effectiveness or cost-effectiveness of new technologies is still incomplete

§  regulatory agencies are pressured to accelerate approval and give faster access to patients, sometimes with less available evidence

§  overarching objective for policy makers to ensure that new value-adding technologies are accessible to patients who need them, while discouraging or stopping to pay for innovations that do not provide value

o   suggestions:

§  rebalancing negotiating powers of buyers and sellers where prices are too high and re-examining costs

·         regulation and reimbursement best approached as cycle comprising collection of real-world evidence, analysis, and review: market authorisation should be granted with explicit conditions and restrictions for use based on what is known at the time, with periodic review based on accumulated evidence of safety and performance or effectiveness

·         ensuring prompt access to treatments for severe diseases without alternative therapeutic options through conditional approval and/or coverage and assessment of products’ performance in real life

·         aligning economic incentives in health care systems to encourage take-up and diffusion of cost-effective technologies and appropriate use (“pay for value”)

§  regulatory framework should be based on clear and explicit set of principles, aligning with broader health care system objectives, social preferences, and economic and social policy

§  processes should be explicit and transparent, and information made publicly available without contravening intellectual property laws or releasing commercially sensitive information

§  regulatory framework relies on strong engagement with all relevant stakeholder groups

·         including experts in relevant clinical areas, economics, finance and bioethics

·         particularly important groups are 1) patients, who bring unique perspectives on impact of specific technology, and 2) citizens, who as custodians of health care system can assist with trade-offs and value judgements

§  better preparing for new technologies through co-operative horizon scanning activities and foresight studies

§  evidentiary requirements for approval of medicines might benefit from international co-operation to avoid duplication and to promote harmonisation of requirements and standards

§  considering new incentives and mechanisms to address gaps in delivering innovations in areas with large unmet needs

-          How OECD health systems define the range of good and services to be financed collectively (2016)

·         societal values as part of criteria for making coverage decisions:

o    in Sweden, the Dental and Pharmaceutical Benefits Board (TLV) makes decisions using three principles including (a) cost-effectiveness principle which means that cost of using medicinal product should be reasonable from medical, humanitarian and socioeconomic perspective, (b) need and solidarity principle, which means that those with most pressing medical needs should have more of health care system’s resources than other patient groups, and (c) human value principle, meaning that health care system should respect equal value of all human life

o    in Australia, sponsors are invited to submit evidence on equity including affordable access and equity assumptions implicit in economic evaluation

o    in Chile, twenty-five health conditions that presented greater mortality and prevalence gaps between socioeconomic groups were selected for health care coverage funded collectively, along with seven other conditions associated with gender and sex inequalities

o    in United Kingdom, NICE must consider impact of its guidance on health inequalities

2.    UNESCO

-          The risks and challenges of neurotechnologies for human rights (2023)

o   rapid introduction of consumer health technology often occurs without sufficient scientific research to back up positive claims of devices and apps, and regulatory responses are slow and difficult to harmonize across globalized markets

o   if consumer health technologies are not sufficiently vetted and validated, unsubstantiated claims to improve health and well-being could harm unsuspecting people, particularly individuals who are vulnerable, for example due to impaired health

o   risk that overreliance on digital technologies, without concomitant building of human capacities to deliver health care in digitized environments, may exacerbate existing “digital divide” and impede access to medical services, especially in socio-economically disadvantaged communities

-          Recommendation on the Ethics of Artificial Intelligence (2021) + UNESCO’s Recommendation on the Ethics of Artificial Intelligence: Key facts (2023)

o   ensure that development and deployment of AI systems related to health in general and mental health in particular, paying due attention to children and youth, is regulated to effect that they are safe, effective, efficient, scientifically and medically proven and enable evidence-based innovation and medical progress

o   actively involve patients and their representatives in all relevant steps of development of digital health interventions

o   pay particular attention in regulating prediction, detection and treatment solutions health care in AI applications by:

(a)  ensuring oversight to minimize and mitigate bias;

(b)  ensuring that professional, patient, caregiver or service user is included as “domain expert” in team in all relevant steps when developing algorithms;

(c)  paying due attention to privacy because of potential need for being medically monitored and ensuring that all relevant national and international data protection requirements are met;

(d)  ensuring effective mechanisms so that those whose personal data is being analysed are aware of and provide informed consent for use and analysis of their data, without preventing access to health care;

(e)  ensuring human care and final decision of diagnosis and treatment are taken always by humans while acknowledging that AI systems can also assist in their work; and

(f)   ensuring, where necessary, review of AI systems by ethical research committee prior to clinical use.

o   develop guidelines for human-robot interactions and their impact on human-human relationships, based on research and directed at future development of robots, and with special attention to mental and physical health of human beings

-          Report of the IBC on ethical issues of neurotechnology (2021)

III.1.5. Accessibility and social justice

78. The problems posed by brain disorders might be seen to present more significant challenges in less developed regions, where they may carry significant stigma and where public health infrastructure and access to treatments for such disorders are very limited. It is therefore desirable that research scientists, technologists, funders and industry partners should work together to develop ways of making access to novel neurotechnology more realistic possibility for those who need it.

79. Since there is a higher incidence of neurological and mental disorders in populations living in poverty, it is foreseeable that there may be increasing demand for the medical applications of neurotechnology among these populations. In such circumstances strong regulations will be needed both to ensure that potential uses of neurotechnology meet the highest bioengineering and medical standards and to prevent deceptive advertising and misuse. These regulations should be developed embracing the principles of responsible innovation, such as ensuring public accountability, inclusiveness, representativeness, enforceability and active participation during the process of both design and application.

80. In contexts of deep social inequality, neurotechnologies might potentially offer a way of compensating those patients suffering from neurological or mental disorders that could have been avoided if they had not had to live in conditions of poverty. Conversely, limitations on access to those technologies would constitute a source of greater inequality. In order to strengthen the former and reduce the possibilities of the latter, it is imperative that access to potentially scarce neurotech-therapies (potentially expensive for low-income countries) be regulated according to fair distributive justice principles such as non-discrimination, highest potential medical benefit, social equity and transparency.

81. The principle of non-discrimination with specific consideration for the particularly vulnerable is expressed in many previous reports of the IBC including […].

-          Report of World Commission on the Ethics of Scientific Knowledge and Technology (COMEST) on Robotics Ethics (2017)

II.4.1. Medical robots

119. […] A major problem is the cost of surgery robots and their maintenance. So actually, the cost of surgery by a robot is higher than with an ‘ordinary surgeon’. The multiplication of robots in surgery will have a consequence on the allocation of resources in public health systems, on the number of surgeons, and on their ability to practise surgery without robots.

-          Report of the IBC on Updating Its Reflection on the Human Genome and Human Rights (2015)

68. Another ethical issue is the cost and affordability of precision medicine (PM). […] However, we are at an early stage in applying PM: its cost is still relatively high, and providing equitable access to it may be difficult even within a single country, due to various levels of health insurance or access to information. It would be unethical if a person was found to be suitable for a treatment, but could not afford it.

In any case, the predictive aspect of genomic data is currently a matter of promise and very few gene mutations or variants are really informative. Cost-benefit analyses are needed to ascertain which procedures have clinical utility and validity and for what diseases. Moreover, it is very important to remember that the development of precision medicine, however promising it may be, should not take place at the expense of neglected diseases such as rare diseases and tropical diseases.

3.    WHO

-          Human genome editing. A framework for governance (2021)

A commitment to equitable access to opportunities and potentially beneficial outcomes from human genome editing for all people, particularly those living in low- and middle-income countries. This includes equitable access to support for health research and for the development of health interventions that are appropriate and affordable for the widest possible range of populations with a view to reducing socioeconomic inequality. It also includes equitable protection from potential coercion, exploitation and other harms.

-          Human genome editing. Recommendations (2021)

WHO should: (i) work with others to encourage relevant patent holders to help ensure equitable access to human genome editing interventions;

WHO and its Director-General should demonstrate both scientific and moral leadership by:

1.    Being open about the opportunities and challenges inherent in human genome editing and communicating these issues in clear, jargon-free, language that is accessible to us all;

2.    Clearly stating the ethical aspects of human genome editing. This will require statements on both somatic and heritable human genome editing. For somatic human genome editing, a statement should address equitable access to the benefits of research and priority setting (for example, sickle-cell disease as a priority). For heritable human genome editing, at a minimum, a statement should reiterate the earlier statement of July 2019; and

3.    Outlining the consequences of failing to address the ethical issues before us if we develop and use technologies without prior careful reflection and intentional collaborative decision-making.

4.    European Commission

-          Addressing health inequalities in the European Union (2020) + Inequalities in access to healthcare - A study of national policies (2018) + Health inequalities in the EU (2013) + Staff Working Document Report on health inequalities in the European Union (2013) + Background Document Solidarity in health: Reducing health inequalities in the EU (2009)

o   impact of social determinants of health

o   Access has three dimensions: coverage, affordability and availability of care. Barriers to access include, for instance, lack of health insurance coverage; high levels of private ('out-of-pocket') healthcare expenditure; geographical disparities in the availability of healthcare services (including infrastructure, equipment, and number of health professionals); waiting times; and cultural obstacles. Household out-of-pocket expenditure can create a financial barrier to access, thus resulting in unmet needs for healthcare. According to Eurostat, more than a quarter of the EU population (aged 15 and over) declared they had an unmet healthcare need in 2014, due to three main reasons: financial costs; travelling distance to care facilities (including transportation problems); or long waiting times.

-          AI and Ethics in the Health Innovation Community (2019) + Ethics Guidelines for Trustworthy AI (2019)

Framework for Trustworthy AI:

1.    Human agency and oversight

2.    Technical robustness and safety

3.    Privacy and data governance

4.    Transparency

5.    Diversity, non-discrimination and fairness

6.    Societal and environmental well-being

7.    Accountability

-          Commission staff working document Accompanying the document Communication from the Commission on enabling the digital transformation of health and care in the Digital Single Market (2018)

The Commission will:

o   Support cooperation to stimulate the supply and uptake of digital health by promoting common principles for validating and certifying health technology.

o   Support theexchange of innovative and best practices, capacity building and technical assistancefor health and care authorities (for using open standards and interoperable digital solutions to promote health, prevent and manage chronic conditions, empower people and centre care on the person) […].

o   Raise awareness aboutinnovative procurement and investment possibilitiesfor digital transformation in public health and healthcare, […].

o   Promote knowledge andskills of citizens, patientsandhealth and care professionalsin using digital solutions in collaboration with health professional organisations and academia.

5.    EGE

-          Statement on Artificial Intelligence, Robotics and ‘Autonomous’ Systems (2018)

(d) Justice, equity, and solidarity

AI should contribute to global justice and equal access to the benefits and advantages that AI, robotics and ‘autonomous’ systems can bring. Discriminatory biases in data sets used to train and run AI systems should be prevented or detected, reported and neutralised at the earliest stage possible.

We need a concerted global effort towards equal access to ‘autonomous’ technologies and fair distribution of benefits and equal opportunities across and within societies. This includes the formulating of new models of fair distribution and benefit sharing apt to respond to the economic transformations caused by automation, digitalisation and AI, ensuring accessibility to core AI technologies, and facilitating training in STEM and digital disciplines, particularly with respect to disadvantaged regions and societal groups.

-          The Ethical Implications of New Health Technologies and Citizen Participation (2015)

o   It has long been acknowledged that health has been unevenly distributed among social groups and that there is a social gradient of health, i.e. the lower a person’s social position, the worse their health. There are concerns that the focus on precision medi­cine could signal an opportunity cost for public health measures at the population, rather than the individual level which are required to achieve heath equity. If there is to be a just and equitable distribution of the po­tential benefits of precision medicine, those contributing data to build large cohorts of patients and healthy indi­viduals will have to be drawn from diverse backgrounds across the socioeconomic spectrum. There is also the question of if and when therapies do become available will they be cost effective and whether the focus will be placed on treatment or prevention? There are varying opinions on whether precision medicine will in fact result in cost savings to the healthcare systems. On the one hand it is argued that tailored effective treatment with less side effects will result in better health outcomes and overall treatment costs will fall. On the other hand, it is argued that developing treatments for small groups of patients will increase the costs of drugs because devel­opmental costs will be borne by fewer patients taking them. This is reflective of the current debate about the cost of novel therapeutics. If precision medicines be­come routinely available, this will likely drive a change in reimbursement policies which many argue will mean that such medicines will become more financially viable for both patients and pharmaceutical companies.

o   If precision medicine is to become part of routine healthcare practice, we will require a workforce that is able to interpret and translate the information it gener­ates into clinical care. There is a current knowledge gap, which will have to be addressed through undergradu­ate and postgraduate training aimed at increasing data literacy skills.

o   The use of individual genetic information may be the cause of new genetic indirect discrimination and in­equitable access to care. From a medical perspective, the use of risk assessment to select patients for additional care is acceptable and justified. But this method may be discriminatory when applied to the general popula­tion, in the context of its application across different age and ethnic groups.

o   An enduring ‘digital divide’ determined by factors such as age, gender, geographical location or socioeconomic status, mean that unequal access to digital technologies as well as highly divergent levels of online literacy persist. This comes alongside additional challenges related to access addressed above.

o   The growing uptake of new health technologies as part of individuals’ everyday healthcare could thus aggravate longstanding health inequalities between different societal groups and across different regions of the world.

o   Citizen involvement can open new avenues for col­lective action and shows potential for rebalancing structural inequalities that have long existed regard­ing investment in medical research. However, it can also exacerbate existing imbalances, amplifying the demands of the well‑resourced and educated, further widening inequities. Breakthrough advances in medical technologies, such as precision medicine, can likewise present public health policy with challenges when setting priorities for investment. Decisions regarding expensive, high‑tech or ‘personalised’ treatments will need to be carefully balanced with wider social needs for essential/basic forms of healthcare.

-          Ethics of information and communication technologies (2012)

o   The growth of new health information technology op­portunities brings a responsibility to design interoper­able, easy to use, engaging, and accessible e‑Health applications that communicate the right information needed to guide health care and health promotion for diverse audiences.

o   The distribution of the benefits and risks of e‑Health must be carefully considered. It is well established that those with lower educational and income levels have worse health. If more healthcare services are shifted to new media, we could leave behind those with limited health literacy or access to technology. Ensuring that new technologies empower people, rather than exac­erbate health inequalities, needs to be at the forefront of the exciting developments in this area.

o   The EGE recognises that disadvantaged and mar­ginalised groups may require different designs, content and applications to suit their specific re­quirements. To this end, the EGE recommends that measures centred around direct provision, subsidies and regulation be examined by the EU to ensure that such groups are not excluded from playing a full and active role in the digital society.

o   The EGE recognises the efforts of the Commission to bridge the digital divide, including collabora­tion with international partners, and recommends that the EU adopts strategies, which go beyond of­fering public access, and incorporate measures to ensure that people can make effective use of the access. This includes providing people with the skills and motivation to harness the potential of ICT through educational and mentoring programmes, which engage the individual in a process of learn­ing, in a way which is meaningful and relevant to them.

-          Ethical aspects of nanomedicine (2007)

o   Access to health-care and new medical technologies is often seen as a challenge for fair health-care systems. Individuals may struggle to gain access to nanomedical innovations, even taking on considerable financial costs. If they cannot afford new diagnostics, drugs, or therapies offered to them, they may feel left behind or even as second-class citizen. Apart from the social question of discrimination and injustice, how do individuals cope with the gap between availability in principle and non-availability in their concrete lives? Simultaneously to the development of new nanomedical diagnostics, drugs, and therapies, this question needs to be addressed as part of a societal and ethical debate. This may also apply to some nanomedical applications.